Flow Cytometry in Double and Triple Hit Lymphomas

Abstract

In a recent article in Cytometry B, Alsuwaidan et al (1) reported that a bright expression of CD38 is highly specific (albeit insensitive) for double and triple hit lymphomas. Their study is interesting and will be of practical value given the current debate over when high-grade lymphoproliferative disorders should be tested for MYC rearrangements, and the fact that these patients appear to benefit from regimens more intense than the standard RCHOP. Finally, given the morphological heterogeneity of these disorders, unconvering flow cytometry markers or combinations that can aid in the diagnosis would be desirable. Based on a patient who recently posed a diagnostic challenge to our flow cytometry unit, we wanted to ask Alsuwaidan et al (1) to provide more data about their cohort with the ultimate goal of optimizing the diagnostic algorithm of these patients. A 55-year-old man with acute respiratory failure due to pleural effusion and middle lobe pneumonia was admitted into the Intensive Care Unit (ICU). The complete blood count and metabolic panel showed a platelet count of 14 × 10/L, white blood cell count of 14 × 10/L, a hemoglobin of 93 g/L, metabolic acidosis, acute renal failure, and serum lactate dehydrogenase (LDH) up to 8 times the upper limit of normal. The peripheral blood smear was notable for 8% circulating blasts and cytospun pleural fluid showed infiltration by lymphoid cells. A computed tomography (CT) scan revealed a large retroperitoneal mass (8 × 7 cm) and thoracic and retroperitoneal adenopathies. Flow cytometry of the pleural fluid, peripheral blood, and bone marrow aspirate found a monotypic (lambda) CD19/CD10-positive population with intense expression of CD38, dim expression of CD45, and loss of B cell markers CD20, CD22, CD79b, and FMC7. CD138 was expressed with moderate intensity (Fig. 1). CD34, CD123, and CD200 were negative. The findings did not seem suggestive of any entity but the working diagnosis (pending the pathological exam of the bone marrow) at the time was plasmablastic lymphoma with aberrant expression of CD10. A center germinal-derived malignancy or, more remotely, acute lymphoblastic leukemia were considered potential diagnostic alternatives. Cytogenetic analysis showed a complex karyotype: 47,X,-Y,del(1)(p36) [3],der(1)del(1)(p36)i(1;?)(q21;?)[7],t(2;3) (q21;q27),+6,del(6)(q13q26),+7,t(8;22) (q24;q11),t(14;18)(q32;q21),der(22)t (1;22)(q21;p11.2)[3][cp10]. Chromosomal rearrangements of BCL2, BCL6, and MYC genes were positive. The patient required orotracheal intubation formechanical ventilation, hemofiltration, and rasburicase for tumor lysis syndrome. He received a course of prephase chemotherapy with methylprednisolone and cyclophosphamide and a course of RCHOP during his stay in the ICU, whence he was subsequently discharged. The bone marrow biopsy showed a diffuse infiltration of blastoids cells with expression of PAX5, CD10, and CD138. The final diagnosis was high-grade B-cell lymphoma with MYC and BCL2 and BCL6 rearrangement, based on the most recent classification of the World Health Organization (WHO). Accordingly, the patient is